School of Chemical, Biological and Environmental Engineering, Oregon State University, Corvallis, OR 97331, USA.
Adv Drug Deliv Rev. 2011 Oct;63(13):1160-71. doi: 10.1016/j.addr.2011.06.015. Epub 2011 Jul 6.
Loss of activity through aggregation and surface-induced denaturation is a significant problem in the production, formulation and administration of therapeutic proteins. Surfactants are commonly used in upstream and downstream processing and drug formulation. However, the effectiveness of a surfactant strongly depends on its mechanism(s) of action and properties of the protein and interfaces. Surfactants can modulate adsorption loss and aggregation by coating interfaces and/or participating in protein-surfactant associations. Minimizing protein loss from colloidal and interfacial interaction requires a fundamental understanding of the molecular factors underlying surfactant effectiveness and mechanism. These concepts provide direction for improvements in the manufacture and finishing of therapeutic proteins. We summarize the roles of surfactants, proteins, and surfactant-protein complexes in modulating interfacial behavior and aggregation. These events depend on surfactant properties that may be quantified using a thermodynamic model, to provide physical/chemical direction for surfactant selection or design, and to effectively reduce aggregation and adsorption loss.
活性丧失是通过聚集和表面诱导变性导致的，这在治疗性蛋白的生产、配方和给药中是一个重大问题。表面活性剂通常用于上下游处理和药物配方中。然而，表面活性剂的有效性强烈取决于其作用机制和蛋白质及界面的特性。表面活性剂可以通过覆盖界面和/或参与蛋白质-表面活性剂的相互作用来调节吸附损失和聚集。要最大限度地减少胶体和界面相互作用中蛋白质的损失，就需要深入了解表面活性剂有效性和作用机制的分子基础。这些概念为治疗性蛋白的制造和后处理提供了改进方向。我们总结了表面活性剂、蛋白质和表面活性剂-蛋白质复合物在调节界面行为和聚集方面的作用。这些事件取决于表面活性剂的性质，可以使用热力学模型进行量化，为表面活性剂的选择或设计提供物理/化学方向，并有效地减少聚集和吸附损失。
